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. 2023 Jul 17;18(1):20220649.
doi: 10.1515/biol-2022-0649. eCollection 2023.

DUSP2 inhibits the progression of lupus nephritis in mice by regulating the STAT3 pathway

Xingzhong Liu  1 , Jie Chen  2 , Lu Liu  3
Affiliations

DUSP2 inhibits the progression of lupus nephritis in mice by regulating the STAT3 pathway

Xingzhong Liu et al. Open Life Sci. .

Abstract

One of the most severe side effects of systemic lupus erythematosus (SLE) is lupus nephritis (LN). To search for potential therapeutic targets in SLE is crucial for the progression of SLE. In this study, we selected C57BL/6J mice as controls and MRL/lpr mice as an LN model and obtained dual specificity phosphatase 2 (DUSP2)-overexpressed mice by injecting AAV-DUSP2 plasmid into the tail vein. Then, proteinuria, urea nitrogen, dsDNA and TNF-α, IL-6, and IL-1β levels were measured in each group of mice. In addition, renal histopathological damage was assessed by hematoxylin-eosin. Finally, STAT3 phosphorylation levels were detected by Western blot assay. The results showed that DUSP2 could reduce proteinuria, urea nitrogen, dsDNA and TNF-α, IL-6, and IL-1β levels and improve renal tissue injury in mice with LN. Mechanistically, DUSP2 inhibited STAT3 phosphorylation. These results demonstrated that DUSP2 played a role in ameliorating LN, which provided potential targets for LN research.

Keywords: DUSP2; STAT3; inflammation; kidney injury; lupus nephritis.

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Conflict of interest statement

Conflict of interest: Authors state no conflict of interest.

Figures

None
Graphical abstract
Figure 1
Figure 1
Low expression of DUSP2 in LN. (a) Expression of DUSP2 in normal and LN kidney tissues obtained from GSE112943 expression profile. (b) The mRNA expression levels of DUSP2 in normal and LN kidney tissues. (c) Protein expression levels of DUSP2 in normal and LN renal tissues. *** P < 0.001 vs control.
Figure 2
Figure 2
DUSP2 ameliorates renal tissue lesions in mice with LN. (a) Expression levels of DUSP2 protein in kidney tissues of various groups of mice. (b) Changes in proteinuria levels of mice in each group from 12 to 20 weeks. (c) Serum urea nitrogen levels in all groups of mice. (d) Serum dsDNA levels in each group of mice. (e) Renal histopathology of mice in each group *** P < 0.001 vs vector.
Figure 3
Figure 3
DUSP2 reduces kidney tissue inflammation in mice with LN. (a) Serum TNF-α, IL-6, IL-1β content of mice in each group. (b) Expression of TNF-α, IL-6, IL-1β mRNA in kidney tissue of mice in each group. *** P < 0.001 vs vector.
Figure 4
Figure 4
DUSP2 inhibits STAT3 activation. Expression of p-STAT3 and COX2 protein in kidney tissue of mice in each group. *** P < 0.001 vs vector.
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